LIPOTEICHOIC ACID STIMULATES LIPOLYSIS AND HEPATIC TRIGLYCERIDE SECRETION IN RATS IN-VIVO

The host response to infection is frequently accompanied by changes in lipid metabolism. Previous studies have shown that endotoxin (LPS), a component of the cell wall of gram-negative bacteria, increases serum lipid levels. In this study, we demonstrate that lipoteichoic acid (L TA), a component of the cell membrane of gram-positive bacteria, also increases serum lipid levels in rats in a dose-dependent manner (0.1-3 00 mu g/200 g body weight). Serum triglyceride levels increased within 2 h after LTA administration with peak values at 4 h (2-fold increase ). Serum cholesterol levels also increased but the effect was delayed occurring at 16 h and was relatively small (1.2-fold increase). LTA (1 0 mu g/200 g BW) did not decrease adipose tissue lipoprotein lipase ac tivity or the clearance of triglyceride-rich lipoproteins. Rather, the LTA-induced hypertriglyceridemia is due to an increase in hepatic tri glyceride secretion. LTA stimulates both hepatic de novo fatty acid sy nthesis and lipolysis. The increased delivery of free fatty acids to t he liver plays a major role in the LTA-induced hypertriglyceridemia. P retreatment with phentolamine, an alpha-adrenergic receptor antagonist , and alprenolol, a beta-adrenergic receptor antagonist, or phentolami ne alone significantly suppressed the hypertriglyceridemia induced by LTA. These adrenergic inhibitors had no significant effect on the incr ease in lipolysis. These results indicate that catecholamines are invo lved in mediating the LTA-induced increase in hepatic triglyceride sec retion via alpha-adrenergic receptors. These changes in lipid metaboli sm may play an important role in the organism's response to gram-posit ive infection.